[Liver organ systems: Valuation by gene expression] [Article in German]

Abstract

The multitude of vital functions of the liver is largely dependent on the complex interaction of hepatocytes with "littoral-cells" and the liver-specific extracellular matrix. In vitro systems used to study the liver are almost exclusively based on the culture of single cells obtained by enzymatic disruption of the essentiel organ structure. In contrast, the slicing technique enables a standardized organ culture, while retaining the intact organ structure. However, previous experiments using this system have been restricted to short-term pharmacological studies and have used general cellular parameters to assess viability. The lack of liver specific validation has hindered the acceptance and application of this organ culture as an alternative to in vivo experiments. In this work we chose the regulation of liver-specific gene expression as an adequate viability criterion because, in contrast to the commonly used general cell physiology parameters, gene expression includes a cascade of differentially coordinated processes. Using hormonal responsiveness of precision-cut liver slices as a basis for comparison, the new developed interphase system was found to be superior to a perfusion system. With the application of this economical and easy-to-handle interphase system, the control of liver-specific gene expression by dexamethasone, cAMP and endotoxin in long-term cultures was found to be modulated in a manner similar to in vivo conditions.